Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stage

Gene expression profiling of colorectal cancer and metastases divides tumours according to their clinicopathological stage
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DOI:
10.1002/path.1606
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发表时间:
2004-09-01
影响因子:
7.3
通讯作者:
Dietmaier, W
Dietmaier, W
中科院分区:
医学1区
文献类型:
--
作者:
Koehler, A;Bataille, F;Dietmaier, W

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匹配的结直肠癌和转移癌的基因表达谱可以揭示与肿瘤进展和转移有关的关键分子事件。使用包含1176个癌症相关基因的基因阵列(Clontech),已经建立了25个结直肠癌(CRC,PT1-4)、相应的正常结肠粘膜和14个肝转移瘤的表达谱。系统聚类法明确区分癌组织和非癌组织,将肿瘤分为高分期(PT4和广泛的淋巴结或远处转移)和低分期(小于或等于topT3)组,并与组织病理学分型有87%(33/38例)相关。大多数原发肿瘤和配对的肝转移瘤聚集在树状图的末端分支上。统计分析(Mann-Whitney U检验)揭示了40个肿瘤特异性基因(29个上调,11个下调),这使得通过聚类分析可以识别恶性组织样本。在匹配的转移瘤中没有发现特定的表达特征,但识别了一组在高和低分期肿瘤中具有统计学意义的表达模式的23个分类基因。这些基因可能是结直肠癌发生的重要靶点,并可能为结直肠癌的治疗提供有用的临床病理工具。版权所有(C)2004年大不列颠和爱尔兰病理学会。作者:John Wiley Sons,Ltd.
Gene expression profiling of matched colorectal carcinomas and metastases could reveal key molecular events involved in tumour progression and metastasis. Expression profiles have been created from 25 colorectal carcinomas (CRCs, pT1-4), corresponding normal colonic mucosa, and 14 liver metastases using cDNA arrays containing 1176 cancer-related genes (Clontech). Hierarchical clustering clearly distinguished carcinomas from non-cancerous tissues, separated tumours into high-stage (pT4 and extensive lymph node or distant metastases) and low-stage (less than or equal topT3) groups, and correlated with the histopathological classification in 87% (33/38 cases). Most primary tumours and matched liver metastases clustered on terminal branches of the dendrogram. Statistical analysis (Mann-Whitney U-test) revealed 40 tumour-specific genes (29 up-regulated, 11 down-regulated) which allowed identification of malignant tissue samples by cluster analysis. A specific expression signature in matching metastases was not found, but a set of 23 classifier genes with statistically significant expression patterns in high- and low-stage tumours was identified. These genes may represent important targets in colorectal carcinogenesis and might provide useful clinicopathological tools in the management of colorectal cancer. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.